Persistent cytomegalovirus infection accelerates non‐complicated obesity‐induced venular inflammation in a mouse model

Cardiovascular diseases (CVD) are the major cause of morbidity and mortality worldwide. In response to CVD risk factors, leukocytes adhere to postcapillary venules in multiple organs before clinical disease develops. Overweight affects 65% of the US population, with half of these considered obese. Obesity is often complicated by other factors, e.g. diabetes, which themselves promote microvascular inflammation, however little is known about whether non‐complicated obesity alters microvascular homeostasis. Cytomegalovirus is a beta‐herpesvirus that infects a majority of people, and has been implicated in CVD. We developed a model to test whether non‐complicated obesity induces leukocyte recruitment and if persistent CMV infection accelerates these responses. C57Bl/6 mice received mock or CMV and at 4 wks post‐infection (wpi) were kept on normal diet or placed on a no cholesterol/low glucose/high fat diet (HFD) for 4–10 wks. The obesity (Lee) index was increased by 4 wks HFD, but blood glucose levels were unchanged. While CMV alone did not alter leukocyte recruitment, leukocyte adhesion in venules was elevated at 8–10 wks HFD. CMV+HFD mice exhibited 2–3 fold increases in leukocyte adhesion and emigration at all timepoints. Our findings suggest that mild obesity induces venular inflammation, which is accelerated by persistent CMV infection before obesity‐associated complications appear. (NIH P20RR018724)